Synthetic route to 2′-deoxy-2′,2′-difluorotetrahydrouridines

A method of producing compound 1:

• or a salt thereof;
• comprising the steps of:
• (a) hydrogenating the starting compound of Formula IV:
• wherein R is a hydroxyl protecting group,
• to produce the compound of Formula IIa:
• (b) reducing the compound of Formula IIa to produce the compound of Formula IIIa:
• (c) deprotecting the compound of Formula IIIa to produce compound 2:
• and
• (d) precipitating or crystallizing compound 2 in the presence of a catalyst to produce compound 1:
• or a salt thereof;
• wherein the catalyst is 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU), acetic acid, trifluoroacetic acid, diisopropylethylamine, or ammonium hydroxide;
• and
• wherein the hydrogenating in step (a) is carried out in the presence of a palladium catalyst.